The intrathecal humoral immune response was analyzed in 83 patients with MS and 35 patients with acute CNS infections. CSF free κ chains and CSF free λ chains were quantified by radioimmunoassay; CSF IgG and albumin were measured by electroimmunodiffusion. The MS patients were characterized by higher levels of free κ chains; free κ: free λ chain ratio; free κ chain:albumin ratio; and IgG:albumin ratio. There were no differences in the level of free λ chains or absolute concentration of IgG. A significant correlation was observed between free κ chains and total IgG in MS and between free κ chains and total IgG in infections, suggesting that the immune response was predominantly IgG-κ in MS and IgG-λ in infections.